Amyloid probes based on Congo Red distinguish between fibrils comprising different peptides

Ashburn, Ted T.; Han, Hogyu; McGuinness, Brian; Lansbury, Peter T.

doi:10.1016/s1074-5521(96)90118-0

Cited by 74 publications

(42 citation statements)

References 26 publications

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“…A previous study also showed that the binding molar ratios of CR molecules to a -type V L dimer were ϳ8 at 40-45°C and ϳ16 at 55°C, measured by gel extraction analysis (22). The dissociation constant (ϳ19 M) of CR binding to SMA is similar to that (ϳ9 M) of CR binding to A␤-amyloid fibrils determined by filtration method using radiolabeled CR (47).…”

Section: Discussionsupporting

confidence: 55%

Congo Red Populates Partially Unfolded States of an Amyloidogenic Protein to Enhance Aggregation and Amyloid Fibril Formation

Kim

Randolph

Manning

et al. 2003

Journal of Biological Chemistry

116

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Congo red (CR) has been reported to inhibit or enhance amyloid fibril formation by several proteins. To gain insight into the mechanism(s) for these apparently paradoxical effects, we studied as a model amyloidogenic protein, a dimeric immunoglobulin light chain variable domain. With a range of molar ratios of CR, i.e. r ‫؍‬ [CR]/[protein dimer], we investigated the aggregation kinetics, conformation, hydrogen-deuterium exchange, and thermal stability of the protein. In addition, we used isothermal titration calorimetry to characterize the thermodynamics of CR binding to the protein. During incubation at 37°C or during thermal scanning, with CR at r ‫؍‬ 0.3, 1.3, and 4.8, protein aggregation was greatly accelerated compared with that measured in the absence of the dye. In contrast, with CR at r ‫؍‬ 8.8, protein unfolding was favored over aggregation. The aggregates formed with CR at r ‫؍‬ 0 or 0.3 were typical amyloid fibrils, but mixtures of amyloid fibrils and amorphous aggregates were formed at r ‫؍‬ 1.3 and 4.8. CR decreased the apparent thermal unfolding temperature of the protein. Furthermore, CR perturbed the tertiary structure of the protein without significantly altering its secondary structure. Consistent with this result, CR also increased the rate of hydrogen-deuterium exchange by the protein. Isothermal titration calorimetry showed that CR binding to the protein was enthalpically driven, indicating that binding was mainly the result of electrostatic interactions. Overall, these results demonstrate that at low concentrations, CR binding to the protein favors a structurally perturbed, aggregation-competent species, resulting in acceleration of fibril formation. At high CR concentration, protein unfolding is favored over aggregation, and fibril formation is inhibited. Because low concentrations of CR can promote amyloid fibril formation, the therapeutic utility of this compound or its analogs to inhibit amyloidoses is questionable.

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Section: Discussionsupporting

confidence: 55%

Congo Red Populates Partially Unfolded States of an Amyloidogenic Protein to Enhance Aggregation and Amyloid Fibril Formation

Kim

Randolph

Manning

et al. 2003

Journal of Biological Chemistry

116

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“…Its absorption spectrum shifts from orange-red to rose-red when it binds to fibrillar Ab1-40. CR binds to amyloid only in the b-pleated sheet conformation (Ashburn et al, 1996;Klunk et al, 1999). Because it has a high affinity for amyloid in brain slices, it is used as a targeting head group which can increase the ability of the complex to bind amyloid plaques in CR-BSA-(Gd-DTPA)n. The ability of CR-BSA-(Gd-DTPA)n to bind Ab protein was demonstrated by the histochemistry staining of APP/PS1 mouse brain sections.…”

Section: Discussionmentioning

confidence: 99%

Detection of Aβ Plaques by a Novel Specific MRI Probe Precursor CR‐BSA‐(Gd‐DTPA)n in APP/PS1 Transgenic Mice

Cui

et al. 2010

The Anatomical Record

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Amyloid plaques are one of the hallmarks of Alzheimer's disease (AD). The lack of specific probes that can detect individual senile plaques in AD has prompted the development of magnetic resonance imaging (MRI) probes. In this study, based on DTPA-gadolinium (III) and congo red (CR), a novel specific MRI probe precursor CR-BSA-(Gd-DTPA)n was successfully synthesized. Its ability to bind to amyloid plaques was evaluated by brain sections from APP/PS1 transgenic mice. Its specificity for Ab plaques was further demonstrated by immunohistochemistry (IHC) staining with the monoclonal antibody to the Ab protein. Meanwhile, the amyloid deposits detected by the CR-BSA-(Gd-DTPA)n were matched to the amyloid deposits detected by Ab specific antibody. We also found that a few amyloid-like deposits which was not detected by IHC. The findings indicated that the probe perhaps could detect the neurofibrillary tangles (NFT) similar to the effect of CR itself, and this will be verified in future experiments. The works suggested that the Ab protein-specific magnetic resonance contrast agent precursor CR-BSA-(Gd-DTPA)n can be used as a potential fluorescence and MR multi-modal imaging probe precursor to display individual senile plaques in AD. Anat Rec, 293:2136Rec, 293: -2143

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“…An analog of CR with two methyl groups at the 2-and 2 0 -positions (2,2 0 -dimethyl-CR) was synthesized from 4-amino-1-naphthalenesulfonic acid sodium salt and 2,2 0 -dimethylbenzidine dihydrochloride (Aldrich) according to the literature method. 13 The crude product was purified by HPLC on a reversed-phase column (Cosmosil 5C18-AR). The sodium salt of unmethylated CR was purchased from Merck.…”

Section: Methodsmentioning

confidence: 99%

“…Examination of the relative affinities of several CR analogs revealed that modification of the naphthalene ring largely affects the affinity for amyloid fibrils. 13 Comparison of amyloid selectivity among CR and related dyes concluded that the central benzidine (4,4-diaminobiphenyl)-type structure of CR is essential for the selective binding to amyloid. 14 Spectroscopic studies provided a few pieces of information on the amyloid-binding sites of CR.…”

Section: Introductionmentioning

confidence: 99%

Binding mode of Congo Red to Alzheimer's amyloid β‐peptide studied by UV Raman spectroscopy

Miura

Yamamiya

Sasaki

et al. 2002

J Raman Spectroscopy

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Congo Red (CR) has long been used for staining amyloid fibrils and recently been found to inhibit amyloid formation. We examined the binding mode of CR to Alzheimer's amyloid b-peptide (Ab) by UV Raman spectroscopy. The 244 nm-excited Raman spectrum of CR exhibits five bands in the 1620-1550 cm −1 region, where C C stretching vibrations of the naphthalene and biphenyl moieties are expected. Among the C C stretching bands, one at 1615 cm −1 becomes weaker and another at 1598 cm −1 gains intensity upon binding to Ab, resulting in a reversal of the relative intensity of the two bands. Concomitant with the intensity reversal, a band at 1158 cm −1 assignable to the N-C stretch becomes stronger. These UV Raman spectral changes are in line with those observed when the fraction of the planar CR molecule is increased by crystallization. Furthermore, opposite spectral changes were observed when the central biphenyl group was methylated to force the two benzene rings in an orthogonal orientation. These observations suggest an increase in planarity of the biphenyl group in the CR-Ab complex. A red shift of the visible absorption is consistent with an expansion of p-conjugation in the planar CR molecule. The torsional mobility of the biphenyl group permitting a planar conformation may be essential for the binding of CR to Ab amyloid fibrils.

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Amyloid probes based on Congo Red distinguish between fibrils comprising different peptides

Cited by 74 publications

References 26 publications

Congo Red Populates Partially Unfolded States of an Amyloidogenic Protein to Enhance Aggregation and Amyloid Fibril Formation

Congo Red Populates Partially Unfolded States of an Amyloidogenic Protein to Enhance Aggregation and Amyloid Fibril Formation

Detection of Aβ Plaques by a Novel Specific MRI Probe Precursor CR‐BSA‐(Gd‐DTPA)n in APP/PS1 Transgenic Mice

Binding mode of Congo Red to Alzheimer's amyloid β‐peptide studied by UV Raman spectroscopy

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